UniProt Accession

 AL4A1_MOUSE; Q8CHT0; B1AXW8; Q7TND0; Q8BXM3; Q8R0N1; Q8R1S2 

Genbank Protein ID

 AK044712; AL831790; CH466615; BC024133; BC026589; BC039281; BC056226 

Genbank Nucleotide ID

 BAC32045.1; CAM21310.1; EDL13315.1; AAH24133.1; AAH26589.1; AAH39281.2; AAH56226.1 

Protein Name

 Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial 

Protein Synonyms/Alias

 P5C dehydrogenase; Aldehyde dehydrogenase family 4 member A1 

Gene Name

 Aldh4a1 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
30	WKHTSSLKVTNEPIL	acetylation	[1, 2]
30	WKHTSSLKVTNEPIL	succinylation	[2]
51	PERDALQKALKDLKG	acetylation	[1, 2, 3, 4]
51	PERDALQKALKDLKG	succinylation	[2]
54	DALQKALKDLKGQME	acetylation	[3]
57	QKALKDLKGQMEAIP	acetylation	[3]
89	SPFNHAHKVAKFCYA	acetylation	[3]
92	NHAHKVAKFCYADKA	acetylation	[1, 2, 3, 4, 5, 6]
92	NHAHKVAKFCYADKA	succinylation	[2]
98	AKFCYADKALLNRAI	acetylation	[1, 2, 3, 4, 5, 7]
98	AKFCYADKALLNRAI	succinylation	[2]
113	DAALAARKEWDLKPM	acetylation	[1, 2, 3, 7]
113	DAALAARKEWDLKPM	succinylation	[2]
118	ARKEWDLKPMADRAQ	acetylation	[1, 3, 4, 5]
129	DRAQVFLKAADMLSG	acetylation	[1, 2, 3, 4, 5]
129	DRAQVFLKAADMLSG	succinylation	[2]
145	RRAEVLAKTMVGQGK	acetylation	[3]
174	DFFRFNAKFAVELEG	acetylation	[1, 2, 4]
174	DFFRFNAKFAVELEG	succinylation	[2]
317	LAGECGGKNFHFVHS	acetylation	[1]
346	AFEYGGQKCSACSRL	acetylation	[2]
346	AFEYGGQKCSACSRL	succinylation	[2]
346	AFEYGGQKCSACSRL	ubiquitination	[8]
357	CSRLYVPKSLWPQIK	acetylation	[1, 2, 3, 4, 5, 9]
357	CSRLYVPKSLWPQIK	succinylation	[2]
364	KSLWPQIKGRLLEEH	acetylation	[1, 2, 3, 4, 5]
364	KSLWPQIKGRLLEEH	succinylation	[2]
375	LEEHSRIKVGDPAED	acetylation	[1]
394	FSAVIDAKAFARIKK	acetylation	[2]
394	FSAVIDAKAFARIKK	succinylation	[2]
401	KAFARIKKWLEHARS	acetylation	[1, 3, 7]
444	DPQEPIMKEEIFGPV	acetylation	[5]
461	VYVYPDDKYRETLQL	acetylation	[1, 2, 4]
461	VYVYPDDKYRETLQL	succinylation	[2]
508	GNFYINDKSTGSVVG	acetylation	[1, 2, 3, 4]
508	GNFYINDKSTGSVVG	succinylation	[2]
508	GNFYINDKSTGSVVG	ubiquitination	[8]
530	RASGTNDKPGGPHYI	acetylation	[1, 3, 4, 10]
530	RASGTNDKPGGPHYI	ubiquitination	[8]
551	QVIKETHKPLGDWRY	acetylation	[1, 2, 3, 4, 5, 11]
551	QVIKETHKPLGDWRY	succinylation	[2]

Reference

 [1] Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.
 Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW.
 Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6. [PMID: 23576753]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [3] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
 Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
 Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
 [4] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
 Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
 J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
 [5] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [6] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [7] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [8] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [9] The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching.
 Yang L, Vaitheesvaran B, Hartil K, Robinson AJ, Hoopmann MR, Eng JK, Kurland IJ, Bruce JE.
 J Proteome Res. 2011 Sep 2;10(9):4134-49. [PMID: 21728379]
 [10] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]
 [11] Circadian acetylome reveals regulation of mitochondrial metabolic pathways.
 Masri S, Patel VR, Eckel-Mahan KL, Peleg S, Forne I, Ladurner AG, Baldi P, Imhof A, Sassone-Corsi P.
 Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3339-44. [PMID: 23341599] 

Functional Description

 Irreversible conversion of delta-1-pyrroline-5- carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes (By similarity). 

Sequence Annotation

 NP_BIND 285 289 NAD.
 ACT_SITE 313 313 Proton acceptor.
 ACT_SITE 347 347 Nucleophile.
 BINDING 207 207 NAD.
 BINDING 232 232 NAD.
 BINDING 446 446 NAD.
 BINDING 512 512 Substrate.
 MOD_RES 98 98 N6-acetyllysine.
 MOD_RES 113 113 N6-acetyllysine.
 MOD_RES 401 401 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Complete proteome; Mitochondrion; NAD; Oxidoreductase; Proline metabolism; Reference proteome; Transit peptide. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 562 AA 

Protein Sequence

Gene Ontology

 GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IDA:MGI.
 GO:0003842; F:1-pyrroline-5-carboxylate dehydrogenase activity; IEA:EC.
 GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IEA:InterPro.
 GO:0006561; P:proline biosynthetic process; IEA:InterPro.
 GO:0010133; P:proline catabolic process to glutamate; IEA:UniProtKB-UniPathway. 

Interpro

 IPR005931; 1-pyrroline-5-COlate_DH.
 IPR016161; Ald_DH/histidinol_DH.
 IPR016163; Ald_DH_C.
 IPR016160; Ald_DH_CS.
 IPR016162; Ald_DH_N.
 IPR015590; Aldehyde_DH_dom. 

Pfam

 PF00171; Aldedh 

SMART

  

PROSITE

 PS00070; ALDEHYDE_DEHYDR_CYS
 PS00687; ALDEHYDE_DEHYDR_GLU 

PRINTS